The human‐specific noncoding RNA RP11‐424G14.1 functions at the intersection of sexually dimorphic pathways in inflammation, senescence, and metabolism
Abstract Sexual dimorphism is a fundamental characteristic of various physiological and pathological processes in humans, including immune responses, senescence, and metabolism. Most studies on the sex bias have focused on sex hormones or female‐biased genes, whereas male‐biased genetic factors rema...
Saved in:
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-02-01
|
| Series: | FASEB BioAdvances |
| Subjects: | |
| Online Access: | https://doi.org/10.1096/fba.2024-00101 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832096745423634432 |
|---|---|
| author | Kameron Kennicott Yun Liang |
| author_facet | Kameron Kennicott Yun Liang |
| author_sort | Kameron Kennicott |
| collection | DOAJ |
| description | Abstract Sexual dimorphism is a fundamental characteristic of various physiological and pathological processes in humans, including immune responses, senescence, and metabolism. Most studies on the sex bias have focused on sex hormones or female‐biased genes, whereas male‐biased genetic factors remain understudied. Here, we show that the Y‐linked noncoding RNA, RP11‐424G14.1, is expressed in human male keratinocytes. Microarray study suggests the NF‐κB pathway as the top biological pathway affected by RP11‐424G14.1 knockdown, consistent with known sex differences in inflammation. Additionally, IGFBP3 is identified as the top gene supported by RP11‐424G14.1 in male keratinocytes. Conversely, in female keratinocytes, IGFBP3 is the top gene repressed by the X‐linked long noncoding RNA XIST, suggesting a central role of IGFBP3 in mediating sexual dimorphism. Knockdown of RP11‐424G14.1 or IGFBP3 in male keratinocytes inhibits cellular senescence, consistent with increased longevity in females. IGFBP3 expression is dependent on insulin, and metabolomics analysis suggests that RP11‐424G14.1 and IGFBP3 regulate acrylcarnitine metabolism. Our study identifies the role of the RP11‐424G14.1‐IGFBP3 pathway in coordinating sex differences in immunity, senescence, and metabolism. With RP11‐424G14.1 being a human‐specific genetic element, our study suggests the evolving feature of sexual dimorphisms in biological processes. |
| format | Article |
| id | doaj-art-5e537d4bd19a4b7996661e4fa51bf1f1 |
| institution | Kabale University |
| issn | 2573-9832 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | FASEB BioAdvances |
| spelling | doaj-art-5e537d4bd19a4b7996661e4fa51bf1f12025-02-05T11:30:18ZengWileyFASEB BioAdvances2573-98322025-02-0172n/an/a10.1096/fba.2024-00101The human‐specific noncoding RNA RP11‐424G14.1 functions at the intersection of sexually dimorphic pathways in inflammation, senescence, and metabolismKameron Kennicott0Yun Liang1Department of Physiology and Pharmacology and Toxicology Michigan State University East Lansing Michigan USADepartment of Physiology and Pharmacology and Toxicology Michigan State University East Lansing Michigan USAAbstract Sexual dimorphism is a fundamental characteristic of various physiological and pathological processes in humans, including immune responses, senescence, and metabolism. Most studies on the sex bias have focused on sex hormones or female‐biased genes, whereas male‐biased genetic factors remain understudied. Here, we show that the Y‐linked noncoding RNA, RP11‐424G14.1, is expressed in human male keratinocytes. Microarray study suggests the NF‐κB pathway as the top biological pathway affected by RP11‐424G14.1 knockdown, consistent with known sex differences in inflammation. Additionally, IGFBP3 is identified as the top gene supported by RP11‐424G14.1 in male keratinocytes. Conversely, in female keratinocytes, IGFBP3 is the top gene repressed by the X‐linked long noncoding RNA XIST, suggesting a central role of IGFBP3 in mediating sexual dimorphism. Knockdown of RP11‐424G14.1 or IGFBP3 in male keratinocytes inhibits cellular senescence, consistent with increased longevity in females. IGFBP3 expression is dependent on insulin, and metabolomics analysis suggests that RP11‐424G14.1 and IGFBP3 regulate acrylcarnitine metabolism. Our study identifies the role of the RP11‐424G14.1‐IGFBP3 pathway in coordinating sex differences in immunity, senescence, and metabolism. With RP11‐424G14.1 being a human‐specific genetic element, our study suggests the evolving feature of sexual dimorphisms in biological processes.https://doi.org/10.1096/fba.2024-00101inflammationmetabolismnoncoding RNAsenescencesexual dimorphism |
| spellingShingle | Kameron Kennicott Yun Liang The human‐specific noncoding RNA RP11‐424G14.1 functions at the intersection of sexually dimorphic pathways in inflammation, senescence, and metabolism FASEB BioAdvances inflammation metabolism noncoding RNA senescence sexual dimorphism |
| title | The human‐specific noncoding RNA RP11‐424G14.1 functions at the intersection of sexually dimorphic pathways in inflammation, senescence, and metabolism |
| title_full | The human‐specific noncoding RNA RP11‐424G14.1 functions at the intersection of sexually dimorphic pathways in inflammation, senescence, and metabolism |
| title_fullStr | The human‐specific noncoding RNA RP11‐424G14.1 functions at the intersection of sexually dimorphic pathways in inflammation, senescence, and metabolism |
| title_full_unstemmed | The human‐specific noncoding RNA RP11‐424G14.1 functions at the intersection of sexually dimorphic pathways in inflammation, senescence, and metabolism |
| title_short | The human‐specific noncoding RNA RP11‐424G14.1 functions at the intersection of sexually dimorphic pathways in inflammation, senescence, and metabolism |
| title_sort | human specific noncoding rna rp11 424g14 1 functions at the intersection of sexually dimorphic pathways in inflammation senescence and metabolism |
| topic | inflammation metabolism noncoding RNA senescence sexual dimorphism |
| url | https://doi.org/10.1096/fba.2024-00101 |
| work_keys_str_mv | AT kameronkennicott thehumanspecificnoncodingrnarp11424g141functionsattheintersectionofsexuallydimorphicpathwaysininflammationsenescenceandmetabolism AT yunliang thehumanspecificnoncodingrnarp11424g141functionsattheintersectionofsexuallydimorphicpathwaysininflammationsenescenceandmetabolism AT kameronkennicott humanspecificnoncodingrnarp11424g141functionsattheintersectionofsexuallydimorphicpathwaysininflammationsenescenceandmetabolism AT yunliang humanspecificnoncodingrnarp11424g141functionsattheintersectionofsexuallydimorphicpathwaysininflammationsenescenceandmetabolism |